This invention relates to the .beta.-lactam antibiotics, the penicillins and the cephalosporins. In particular, this invention relates to 6-alkoxylated 6-acylamidopenicillanic acids and 7-alkoxylated 7-acylamidocephalosporins and to a process for the preparation thereof.
Numerous penicillin and cephalosporin antibiotics have been prepared by semi-synthetic means. For example, the nucleus of penicillin, 6-aminopenicillanic acid (6-APA), has been acylated with a wide variety of acylating agents to obtain active pencillin antibiotics. Likewise, the cephalosporin nucleus, 7-aminocephalosporanic acid (7-ACA), has been derivatized in like manner to provide a wide variety of biologically active 7-acylamidocephalosporanic acids. Further, the semi-synthetic nucleus of the cephalosporin antibiotics, 7-aminodeacetoxycephalosporanic acid (7-ADCA), has been acylated with a wide variety of acyl moieties to provide active 7-acylamidodeacetoxycephalosporanic acids. More recently, the cephalosporin nucleus which bears a 3-acetoxymethyl substituent has been further derivatized by the replacement of the acetoxy group with a wide variety of substituents.
Heretofore, cephalosporins and penicillins bearing a substituent on a carbon of the .beta.-lactam ring have been little described in the literature.
7-Methoxycephalosporin C and 7-(5-amino-5-carboxyvaleramido)-7-methoxy-3-carbamoyloxymethyl-3-cephem-4- carboxylic acid obtained from the fermentation of Streptomyces lipmanii and Streptomyces clavuligerus are described in J. Am. Chem. Soc. 93, 2308 (1971). 6-Methylpenicillin has been suggested by Strominger, Amer. J. Med., 39, 708 (1965).
It is an object of this invention to provide novel derivatives of cephalosporin and penicillin antibiotics. It is a further object of this invention to provide 6-alkoxy-6-acylamido penicillanic acids and 7-alkoxy-7-acylamidocephalosporanic acids and deacetoxycephalosporanic acids. It is also an object of this invention to provide a process for the preparation of substituted cephalosporins and penicillins wherein the substituent group is introduced into the 6- and 7-positions of the penicillin and cephalosporin nuclei, respectively.